In the field of chromatography, spheroid polymer particles are widely used as packing material to form chromatographic columns. Generally chromatographic materials can be silica based or polymer based. The shape of these particles can be irregular or spherical. The particles may be porous, superficially porous or non-porous. More recently monolithic materials based on silica or polymer have been developed which consist of ‘one porous block’ of material.
The characteristics of chromatographic action of the packed spheroid particles are in one aspect related to the size distribution of the particles. Other aspects of separation by chromatography encompass certain surface characteristics such as functional groups (in fact: the chemical character of the surface), physical character of the surface (e.g. vacancies in the surface area, morphology, adhesion aspects etc.).
In general the following characteristics may apply to a chromatographic material:                the particle shape: spherical particles are more easy to pack into a column giving a more homogeneous packing bed, thus generating a better separation performance.        the particle size: in general smaller particles generate sharper peaks and a better separation efficiency, but they generate a higher backpressure (resistance to flow through the column).        pore size and pore volume: a porous structure generates internal surface, thus enlarging the effective chromatographic surface.        
Often, when relatively large compounds like biomolecules are to be separated on a porous material, there is a need for very large pores to allow unhindered diffusion of the compounds in and out of the pores. Small pores or pores with sizes in the range of the separated compounds may give a hindered diffusion in and out of the pores. This will result in broad peaks and a less efficient separation. However, the need for these very large pores to allow unhindered diffusion may induce another drawback. As the pores in a chromatographic material become larger the material may become mechanically weaker. At high pressure such as in long columns and/or at high flow rates the particles may crush.
Polymer particles for use as chromatographic material are usually prepared by so-called dispersion polymerization, also referred to as suspension polymerization (E. Erbay and O. Okay, J. Appl. Poly. Sci. 71, (1999)1055-1062). During this process little globules of polymer precursors are formed, which consist of monomers dissolved in an appropriate organic solvent, which nuclei are dispersed in a water based medium, so that an oil-in-water dispersion is present, wherein the organic phase is the discontinuous medium and water is the continuous medium.
A generally recognized drawback of dispersion polymerization is that dispersion polymerization leads to particles having a widely spread size distribution, also referred to as a broad size distribution. See e.g. the above article from E. Erbay and O. Okay and further Kithara et al., Anal. Sci., Vol 17 supplement 2001, p. 1225-1228), Coutinho et al., Eur. Polym. J., 31, (1995), p. 1243-1250. The art has proposed to solve this issue by performing a tedious size classification step after the actual polymerization, which can be roughly interpreted as an act of sieving, or size selection. See e.g. U.S. Pat. Nos. 5,130,343 and 6,533,939, as well as EP 0 534 057. An alternative solution that has been used is to use specifically sized seed particles from which the particles grow. See also e.g. U.S. Pat. No. 6,855,761.
There is a general need for a more uniform—or, in other words, narrow—size distribution of products obtained by dispersion polymerization, because the narrower the size distribution of particles, the better their chromatographic performance.
The size distribution is dealt with in detail in this description later under the section summary of the invention, but for now it is important to introduce the ratio F being a measure for size distribution that is used in respect of the present polymer particles. It is generally accepted in the field of chromatography that this ratio F preferably should be of a value of 2 or lower. This ratio can be achieved by either of the above two methods of classification and seeding. Here it is noted that one can also perform chromatography when F< or > than 2. However, when too many little particles are present the backpressure of a chromatographic column will rise. When too many large particles are present the separation efficiency will drop.
The invention aims at improving the preparation of the above particles by providing a novel method by which the preparation can be performed in a relatively easy manner. In particular, it is an object of the invention to provide such a method wherein a tedious classification step or the use of seed particles as required in prior art methods to achieve a required size distribution of the polymer particles prepared may be omitted thereby reducing the costs. Also other objectives are set which are complied with, as will be explained infra.